Using techniques of molecular cloning, nucleotide acid hybridization, and nucleotide sequencing, more than 50 retrovirus-like DNA segments have been cloned from a human gene library. Work carried on during the past year indicates that the major class of endogenous, retrovirus-like DNA can be divided into two closely related families each of which is represented 35-50 times per haploid mass of human DNA. One family consists of typical full-length retroviral sequences including segments that encode gag, pol, and env gene products; its termini contain cross-reactive 500 bp elements that have features characteristic of retroviral LTRs. Each LTR contains an imperfect inverted complementary repeat (6 or 7 out of 10 match), a putative TATA box, a typical polyadenylation signal, a possible CCAAT sequence, and a 13 bp polypurine tract. A potential tRNA primer binding site that follows the 5' LTR is a 16/18 or a 17/18 match with the 3' end of a rat glutamic acid tRNA. The second family of endogenous retroviral sequences contains 4.1kb of gag and pol sequences that are very similar to those present in the full-length clones. The truncated family, however, is not bounded by LTRs nor does it contain any env sequences. Instead, the retroviral sequences are flanked by a tandem array of imperfect repeats 72-76 bp in length. Further analyis os several human retroviral clones indicted that large blocks of DNA involving both viral and flanking cellular DNA sequences have been amplified subsequent to the integration of viral DNA into the human chromosome during the early phases of viral infection. Southern blot hybridization was used, in one instance, to demonstrate that at least one amplification event occurred prior to the divergence of man and chimpanzee since similar recruited restriction enzyme fragments could be detected in the DNAs of these two primates. Other hybridization experiments employing somatic cell hybrids indicated that copies of retroviral segments were present or several different human chromosomes.